Personalized Therapy in Non-small Cell Lung Cancer (PTINCLC)

• ClinicalTrials.gov Identifier: NCT01781988
• Recruitment Status: Completed
• First Posted: February 1, 2013
• Last Update Posted: December 17, 2014
• Sponsor: Guangzhou Medical University
• Collaborator: The First Affiliated Hospital of Guangzhou Medical University
• Information provided by (Responsible Party): Heyuwen, Guangzhou Medical University

Study Description

Brief Summary:

Excision repair cross complementing 1 (ERCC1) ribonucleotide reductase M1 (RRM1) and thymidylate synthase(TS) are molecular determinants that predict sensitivity or resistance to platinum agents 、 gemcitabine and pemetrexed respectively.

Tailored therapy using these molecular determinants suggested patient benefit in a previously reported phase 2 trial. Here, we designed a study for an individual patient analysis of prospectively accrued patients who were treated with the "personalized therapy" approach versus other standard approaches.

Condition or disease	Intervention/treatment	Phase
Lung Cancer; Carboplatin Adverse Reaction	Drug: carboplatin, gemcitabine , pametrexed	Phase 2

Detailed Description:

Patients who had nonsmall- cell lung cancer (NSCLC) performance status of 0/1 were accrued to 2 phase 2 clinical trials Trial A (carboplatin and chemotherapy individuation based on sensitivity marker ), Trial B (carboplatin non-individuation or chemotherapy non-individuation ).

Patients who were treated on Trials B were analyzed as the "standard therapy" group. Patients accrued to Trial A were called the "personalized therapy" group. disease free survival (DFS) was estimated using the Kaplan-Meier method.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 128 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Clinical Study of Personalized Therapy for Non-small Cell Lung Cancer Based on ERCC1/RRM1/TS Expression
• Study Start Date: June 2009
• Actual Primary Completion Date: December 2014
• Actual Study Completion Date: December 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: A.individual therapy; Carboplatin was administrated at an area under the plasma concentration time curve (AUC) of 5 on day 1 every 21 days, while gemcitabine was administrated at a dose of 1250 mg/m2 on day 1 and 8 and pemetrexed was administrated at a dose of 500 mg/m2 on day 1.	Drug: carboplatin, gemcitabine , pametrexed; A.individual therapy :enrolled patients with ERCC1 negative tumors who received carboplatin and a third-generation agent (gemcitabine or pametrexed) based on RRM1 or TS expression. If RRM1 protein was negatively expressed in the tumor tissues, gemcitabine was used, whereas pemetrexed was used if RRM1 was positively expressed and TS was negatively expressed. B.non-individualized therapy :enrolled patients who received carboplatin and a third-generation agent but were not based on ERCC1, RRM1, or TS expression.
Experimental: B. non-individualized therapy; Carboplatin was administrated at an area under the plasma concentration time curve (AUC) of 5 on day 1 every 21 days, while gemcitabine was administrated at a dose of 1250 mg/m2 on day 1 and 8 and pemetrexed was administrated at a dose of 500 mg/m2 on day 1.	Drug: carboplatin, gemcitabine , pametrexed; A.individual therapy :enrolled patients with ERCC1 negative tumors who received carboplatin and a third-generation agent (gemcitabine or pametrexed) based on RRM1 or TS expression. If RRM1 protein was negatively expressed in the tumor tissues, gemcitabine was used, whereas pemetrexed was used if RRM1 was positively expressed and TS was negatively expressed. B.non-individualized therapy :enrolled patients who received carboplatin and a third-generation agent but were not based on ERCC1, RRM1, or TS expression.

Outcome Measures

Primary Outcome Measures :

1. The disease-free survival [ Time Frame: Followed up these patients for disease-free survival for 4 years ]
   The disease-free survival was measured from the day of tumor resection until tumor recurrence (progression) or death as the end point

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Histologically confirmed non-small cell lung cancer
2. age from 18 years to 75 years
3. ECOG Performance Status no more than 2
4. at least one appraisable lung focus of diameter≥ 10 mm by lung CT
5. Haemoglobin ≥10.0 g/dl, Absolute neutrophil count ≥(ANC) 1.5 x 109/L, platelets ≥100 x 109/L
6. Total bilirubin ≤1.5 x upper limit of normal (ULN)
7. ALT and AST < 2.5 x ULN in the absence of liver metastases, or < 5 x ULN in case of liver metastases
8. Creatinine clearance ≥60ml/min (calculated according to Cockcroft-gault formula)
9. Informed consent should be obtained before treatment.

Exclusion Criteria:

1. Mixed non-adenocarcinoma cell lung cancer histology
2. Previous treatment for Systemic chemotherapy or local radiotherapy
3. Be allergic to chemotherapy drugs
4. second active primary malignancy or serious concomitant medical disease
5. difficulties with adequate follow-up

Contacts and Locations

Locations

China, Guangdong

The first affiliated hospital of Guangzhou MC

Guangzhou, Guangdong, China, 510120

Sponsors and Collaborators

Guangzhou Medical University

The First Affiliated Hospital of Guangzhou Medical University

Investigators

• Study Chair: Jianxing He, Proressor; The first affiliated hospital of Guangzhou MC

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

He YW, Zhao ML, Yang XY, Zeng J, Deng QH, He JX. Prognostic value of ERCC1, RRM1, and TS proteins in patients with resected non-small cell lung cancer. Cancer Chemother Pharmacol. 2015 Apr;75(4):861-7. doi: 10.1007/s00280-015-2714-y. Epub 2015 Mar 3.

• Responsible Party: Heyuwen, Yuwen He, MD, Guangzhou Medical University
• ClinicalTrials.gov Identifier: NCT01781988
• Other Study ID Numbers: GZMC12521; PT12521 ( Other Identifier: The First Affiliated Hospital of Guangzhou Medical University )
• First Posted: February 1, 2013
• Last Update Posted: December 17, 2014
• Last Verified: December 2014

Keywords provided by Heyuwen, Guangzhou Medical University:

lung cancer; gemcitabine; carboplatin; pemetrexed

Additional relevant MeSH terms:

Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Gemcitabine; Carboplatin; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs